Olfactory Support Cells

嗅觉支持细胞

• 批准号: 7738592
• 负责人: Timothy S McClintock
• 金额: $ 18.56万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7738592
• 关键词: Abbreviations; Acinar Cell; Afferent Neurons; Aging; Animals; Apoptotic; Binding; Bioinformatics; Biological Process; Cell Adhesion; Cell physiology; Cell secretion; Cells; Chemicals; DNA; Data; Data Set; Databases; Detection; Disease; Environment; Epithelium; Family; Fluorescence-Activated Cell Sorting; Gene Expression; Genes; Gland; Green Fluorescent Proteins; Immune; In Situ Hybridization; Ion Transport; Knock-out; Knowledge; LacZ Genes; Lead; Longevity; Messenger RNA; Molecular; Molecular Profiling; Mouse Strains; Mucous body substance; Mus; Neurons; Odors; Olfactory Epithelium; Olfactory Nerve; Outcome; Pathway interactions; Pattern; Phagocytosis; Probability; Receptor Protein-Tyrosine Kinases; Reporter; Retinal Degeneration; Sampling; Signal Pathway; Signal Transduction; Site; Structure of respiratory epithelium; Supporting Cell; System; Testing; Tissues; Xenobiotics; afferent nerve; age related; axl receptor tyrosine kinase; cell type; directed attention; improved; postnatal; public health relevance; receptor; recombinase; relating to nervous system; reproductive; research study; sustentacular cell

Description (provided by applicant): The support cells of the olfactory epithelium have received little direct attention, yet several lines of evidence indicate that they are critical for maintaining or regulating the olfactory sensory nerve cells, the ongoing replacement of olfactory sensory nerve cells, and the local environment that allows odor detection. A detailed molecular understanding of the two major types of support cells, sustentacular cells and Bowman's gland cells, is lacking. Fortuitously, we have developed a mouse strain that will allow us to extract two dissociated cell samples: One highly enriched for sustentacular cells, the other for Bowman's gland acinar cells. Aim 1 will therefore investigate whether two support cell transcriptomes show overrepresentation of biological processes hypothesized to be active in these support cells: Clearance of foreign chemicals, cell adhesion, clearance of dying cells, secretion, and certain cell signaling pathways. The outcome of this aim will also include a database of the probability of expression in sustentacular cells and Bowman's gland acinar cells for more than 10,000 genes. Aim 2 delves more deeply into a mechanism we hypothesize controls phagocytosis by sustentacular cells, one of the few documented functions of these cells. We hypothesize that signaling through the receptor tyrosine kinase Tyro3 regulates clearance of dying nerve cells by sustentacular cells. Overall, this project is another step toward a complete understanding of gene expression patterns in the olfactory epithelium and will identify most functions present in the little-studied support cells of this tissue. In addition, these experiments are relevant to age-dependent loss of olfactory function because deficits in Tyro3 receptor family signaling in the support cells of several other tissues are known to lead to age-related disorders, such as retinal degeneration. PUBLIC HEALTH RELEVANCE: The olfactory system has evolved to detect and discriminate many thousands of distinct volatile chemicals, in part by generating a favorable microenvironment and retaining the ability to replace damaged olfactory nerve cells even as aging occurs. Investigating how the support cells of the epithelium contribute to odor detection and nerve cell replacement is bound to improve our understanding of how cellular interactions contribute to the ability of the olfactory system to function throughout an animal's life span. This project investigates the molecular capabilities of the support cells of the epithelium and a hypothesized mechanism by which support cells clear dying nerve cells to make way for new nerve cells.

描述（由申请人提供）：嗅觉上皮的支持细胞很少受到直接关注，但一些证据表明它们对于维持或调节嗅觉感觉神经细胞、嗅觉感觉神经细胞的持续更新和允许气味检测的当地环境。目前缺乏对两种主要类型的支持细胞（支持细胞和鲍曼腺细胞）的详细分子了解。幸运的是，我们开发了一种小鼠品系，使我们能够提取两种分离的细胞样本：一种高度富集维持细胞，另一种富含鲍曼氏腺腺泡细胞。因此，目标 1 将研究两个支持细胞转录组是否表现出假设在这些支持细胞中活跃的生物过程的过度表现：外来化学物质的清除、细胞粘附、垂死细胞的清除、分泌和某些细胞信号传导途径。这一目标的成果还将包括一个关于 10,000 多个基因在支持细胞和鲍曼腺腺泡细胞中表达概率的数据库。目标 2 更深入地研究了我们假设的控制维持细胞吞噬作用的机制，这是这些细胞为数不多的有记录的功能之一。我们假设通过受体酪氨酸激酶 Tyro3 发出的信号调节维持细胞对垂死神经细胞的清除。总体而言，该项目是全面了解嗅觉上皮基因表达模式的又一步，并将识别该组织中研究很少的支持细胞中存在的大多数功能。此外，这些实验与年龄依赖性嗅觉功能丧失有关，因为已知几种其他组织的支持细胞中 Tyro3 受体家族信号传导的缺陷会导致与年龄相关的疾病，例如视网膜变性。公共健康相关性：嗅觉系统已经发展到能够检测和区分数千种不同的挥发性化学物质，部分原因是产生有利的微环境，并保留在衰老时替换受损嗅觉神经细胞的能力。研究上皮支持细胞如何促进气味检测和神经细胞替代，必将提高我们对细胞相互作用如何促进嗅觉系统在动物整个生命周期中发挥作用的能力的理解。该项目研究了上皮支持细胞的分子能力，以及支持细胞清除垂死神经细胞为新神经细胞让路的假设机制。